The inflammatory myopathies are a heterogeneous group of diseases which have been suspected of having an autoimmune basis. Intensive work in the past ten years in our laboratory, as well as others, has revealed the presence of disease specific antibodies which relate certain autoantibodies to specific disease subsets. Thus, antibodies to Jol (histidyl tRNA synthetase) occur principally in polymyositis associated with interstitial lung disease. Antibodies to other translation related proteins (as yet of unidentified function) also seem to be associated with this clinical picture. Antibodies to Mi2, a nuclear antigen of unknown function occur primarily in patients with dermatomyositis while antibodies to Pm- Scl, a nucleolar antigen, occur in patients most frequently with polymyositis-scleroderma overlap. We propose to build on these findings by improving the immunoassays for these serological reactions, determining the molecular structure and function of the antigens, and further determining the clinical diagnostic specificity of these reactions. The relationship of the titer of these antibodies to the severity and activity of the disease will also be studied. In addition, systematic HLA studies will be performed so that genetic factors related to specific autoantibody production can be ascertained. Finally, the hypothesis that infection with picornaviruses may be an important initiating event in these diseases will be explored by determining if 1) autoantibodies to translation related proteins can bind picornaviral RNA in immunoprecipitation studies and conversely if 2) convalescent sera from patients with picornavirus infection can inhibit translation related proteins which are known to be targets of autoimmunity in polymyositis patients.